Plants and animals have to survive in a world laden with pathogenic, bacteria and fungi. Numerous fungi and bacteria are serious pests of both agricultural crops and mammals. Yet, despite the pathogens which are encountered daily, organisms display an uncanny survivability. Thc resilience displayed by diverse organisms can be attributed to the presence of a repertoire of host defense organisms.
In animals, including humans, defense may be mediated by events such as immune response, complement activation, phagocytosis, and release of small molecular weight antimicrobial peptides. I-lowever, in insects, amphibians, and other lower organisms, although comparable immune responses are less well characterized, it is clear that small molecular weight peptides play a major role in warding off infection.
Plants display apparent protective mechanisms in response to pathogens. Such responses include the production of proteins that alter extracurricular matrix of the host, such as extensins and glycine-rich proteins. Additionally, plants produce proteins that are directly involved with antimicrobial activity, such as glucanases and chitinases, protease inhibitors, and enzymes associated with phytoalexin biosynthesis.
Various antimicrobial peptides have been isolated from many different kinds of organisms, such as bacteria, insects, mammals, amphibians and plants. Examples include linear peptides, such as secropin, magainin and melittin, as well as tachyplesin, and members of the defensin family.
Tachyplesin is a naturally occurring cationic antimicrobial peptide that is seventeen (17) residues long. The peptide has an amidated carboxy terminus and contains two disulfide bridges. The antimicrobial activity of the molecule has been attributed to an amphipathic structure consisting of two anti-parallel P-sheets held ridged by the disulfide bonds and beta turn.
U.S. Pat. No. 5,580,852 discloses derivatives of the peptide tachyplesin which have potent anti-fungal activity against common plant pathogens. Specific amino acids sequences are set forth as having plant pathogenic fungi and seed pathogen activity. However, there is no method set forth in the application whereby amino substitutions can be made and activity predicted. In fact, there is no a priori method of predicting that any given protein will function. Each protein is unique, and this necessarily has to be an experimental determination. The scientific literature is replete with examples for seemingly conservative substitutions that have resulted in major perturbations of structure and activity.
Because of the pathogens facing both the plant and animal world, new antimicrobial peptides are needed. Furthermore, there is needed a method to predict the activity of new derivatives of tachyplesin proteins.